New Surgical Technique to Induce Reversible Liver Fibrosis by Surgical Closure of Major Duodenal Orifice in Dogs

This study was conducted to induce and evaluate reversible liver fibrosis in dogs by surgical closure of the major duodenal orifice. The study was performed on six healthy local adult dogs. Reversible liver fibrosis was surgically induced in all animals by surgical closure of major duodenal papilla using absorbable suture material for 60 days. Induced liver fibrosis was assessed by clinical, ultrasonographical examination, laboratory and histological methods. The clinical manifestation of the jaundiced dogs showed reduced food intake, pale-yellowish mucus membrane, inflammatory signs of the wound site and severe postoperative pain. Biochemically, there was significantly increased values of the aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, indirect bilirubin, direct bilirubin and total bilirubin especially during the first two days after surgery followed by a gradual decrease of these values until the end of the but still higher than normal values. Ultrasonographic examinations showed abnormal changes in the liver tissue such as an increase in both size and wall thickness of the gall bladder and mottled heterogeneous appearance of the liver during the first two weeks following the surgical induction of the hepatic fibrosis. Histological evaluation of liver samples revealed showed necrosis of hepatocytes and deposition of eosinophilic material, infiltration of inflammatory cells, recent thrombus in the hepatic vein, fatty change. Slight clinical, biochemical, ultrasonographic improvement was observed at 30th post-operative day. In conclusion, surgical induction of reversible liver fibrosis in dogs was an easy technique by surgical closure of major duodenal papilla and the results were confirmed by the clinical, ultrasonographical, laboratory and histological examination.

Predictors of the development of hepatorenal syndrome

Objective. To identify the predictors of the development of hepatorenal syndrome in patients with liver cirrhosis.Materials and methods. We analyzed the medical records of 79 patients diagnosed with liver cirrhosis. The laboratory research included general and biochemical blood tests. The general blood test measured erythrocyte and leukocyte counts. The biochemical blood test measured the content of ALT (U/L), AST (E/L), total bilirubin (μmol/L), direct bilirubin (μmol/L), indirect bilirubin (μmol/L), alkaline phosphatase (U/L), albumin (g/L), urea (mmol/L), creatinine (mmol/L), cholesterol (mmol/L).Viral hepatitis markers were determined for all the patients.Results. The predictors of the development of hepatorenal syndrome were identified: increased leukocyte count, increased total and indirect bilirubin levels, urea level and decreased erythrocyte count and albumin level. The most specific predictors were the amount of indirect bilirubin (98 %) and the content of albumin in the serum (89.8 %), and the most sensitive predictors were AST (96.7 %) and the content of red blood cells and creatinine (73.3 %).Conclusion. The most significant predictors of the development obtained will contribute to the diagnosis of the development of hepatorenal syndrome in patients with liver cirrhosis.

Alterations in Various Biochemical Parameters Among Covid-19 Patients: An Observational Retrospective Analysis

Novel coronavirus causing the pandemic infectious disease termed as COVID-19 is characterized by respiratory illness which may lead on to acute respiratory distress syndrome. Ferritin is a key mediator of immune dysregulation leading on to cytokine storm. Alterations in various biochemical parameters have been widely reported in COVID-19. Early identification of effective biomarkers to assess the severity of this disease is essential. Our study was aimed to evaluate the variations in the routinely analysed biochemical parameters and their association with ferritin levels among COVID patients. The study participants consisted of 270 members among which 149 were COVID positive and 121 were negative. Analysis of the routine biochemical parameters as well as ferritin level were carried out. Among the 149 positive cases, 84 (56.4%) were mild positive with ferritin levels <500ng/ml and 65 (43.6%) were severe positive with ferritin levels >500ng/ml. We reported significant increase in serum ferritin levels in severe positive samples (1449.84 ± 249.47) compared to mild positive samples (230.04 ± 17.41). We observed increased levels of total bilirubin in 12.7%, direct bilirubin in 16.8%, indirect bilirubin in 8.7%, AST in 65.8%, ALT in 44.3%, ALP in 9.4%, GGT in 51.7%, urea in 18.4%, creatinine in 14.3%, BUN in 18.4% and decreased levels of total protein and albumin in 23.5% positive patients compared to negative patients. Ferritin and its associated biochemical parameters act as predictors of COVID severity. These biochemical alterations suggest the significance of early risk assessment and monitoring of COVID patients.

Graves Disease (Thyroid Storm) with Polyautoimmune Disorders (Autoimmune Hemolytic Anemia and Probable Autoimmune Hepatitis)

Graves' disease is caused by IgG antibodies that bind to the Thyroid Stimulating Hormone (TSH) receptor on the surfaceof the thyroid gland. These bonds drive the growth of stimulated thyroid follicular cells causing the glands to enlarge andincrease the production of thyroid hormones. Previous studies mention the association of HLA-B8 and HLA-DR3 withGraves' disease and the Cytotoxic T-lymphocyte-associated-4 (CTLA-4) gene on chromosome 2q33 as a result of reducingT-cell regulation, resulting in autoimmune disease. Autoimmune thyroid disease is often found together with otherautoimmune disorders (polyautoimmune). A 51-year-old male complained of dyspnea, yellowing of the body, and a lumpon the neck. One year ago, he was diagnosed with hyperthyroidism. Graves' disease was suspected due to a score of 22 forthe Wayne index, FT4 96.9 pmol/L, TSHs <0.01 μIU/mL, TRAb 10.8 IU/L, thyroid uptake test for toxic diffuse struma. Inaddition, the patient had atrial fibrillation and a thyroid storm with a Bruch Wartofsky index score of 65. Laboratoryexamination found normocytic normochromic anemia, thrombocytopenia, reticulocytosis, direct coomb test and autocontrol results positive one, SGOT 87 U/L, SGPT 59 U/L, alkali phosphatase 166 U/L, total bilirubin 38.13 mg/dL, directbilirubin 16.59 mg/dL, indirect bilirubin 21.54, LDH 318 U/L, establishing the diagnosis of Autoimmune Hemolytic Anemia(AIHA). Autoimmune hepatitis score: 15, so a diagnosis of probable autoimmune hepatitis was made.

A full-term pregnant woman with secondary Evans syndrome caused by severe coronavirus disease 2019: a case report

Background In this report, we describe a very challenging case of a patient with secondary Evans syndrome caused by severe coronavirus disease 2019 infection in a pregnant full-term woman. Case presentation A 29-year-old full-term pregnant Indonesian woman presented with gross hematuria, dry cough, fever, dyspnea, nausea, anosmia, and fatigue 5 days after confirmation of coronavirus disease 2019 infection. Laboratory examinations showed very severe thrombocytopenia, increased indirect bilirubin, and a positive direct Coombs’ test. From peripheral blood, there was an increased number of spherocytes, which indicated an autoimmune hemolytic process. Antinuclear antibody and anti-double-stranded DNA test results were negative, and her virology serological markers are also negative for human immunodeficiency virus, cytomegalovirus, and hepatitis B and C. Despite aggressive treatment with platelet transfusion, high-dose steroid, and thrombopoietin receptor agonists, the platelet count did not recover, and a speculative cesarean delivery had to be done with a very low platelet count.

Clinical Characteristics of Choledochal Cysts With Intrahepatic Bile Duct Dilatations

Background: Whether the dilated intrahepatic bile duct (IHBD) has any effect on prognosis of choledochal cyst (CC) remains controversy. In the study, we aim to summarize the clinical characteristics and prognosis of those patients.Methods: A total of 192 children (47 males, 145 females) diagnosed with CC were identified in our hospital, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics of group B based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were significantly increased in group B (p=0.01 and 0.033, respectively). Preoperative total bilirubin (TB), direct bilirubin (DB), and indirect bilirubin (IDB) were also higher in group B than in group A (p=0.0052, 0.0005, and 0.0136, respectively), as were preoperative levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and total bile acid (TBA) (p=0.0057, 0.0250, 0.0002, and 0.0242, respectively). Early postoperative GGT levels in group B remained abnormal and were significantly higher than in group A (p=0.0003). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (p=0.012) and also occurred earlier in group B (p<0.001), among them, dilated IHBDs recovered to normal in 89.23% (7/65) of patients. Meanwhile, the incidence of postoperative pancreatitis increased significantly in group B as well (p=0.003).Conclusion: CC with IHBD dilatation was associated with significantly increased preoperative bilirubin levels, abnormal liver function, and higher incidence of liver fibrosis or cirrhosis early in the disease course. Timely radical surgery is recommended for such patients and postoperative extinction of the IHBD dilatation occurs early in most of those patients.

Serum bilirubin levels are associated with poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack

Background The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods All patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2–6 and 3–6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes. Results Among 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90–17.70), 3.80 (2.70–5.30), and 9.30 (6.70–12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2–6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19–1.59) and 1 year (OR, 1.31; 95 % CI, 1.13–1.52), and mRS score 3–6 at 3 months (OR, 1.33; 95 % CI, 1.11–1.59) and 1 year (OR, 1.28; 95 % CI, 1.07–1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome. Conclusions Elevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year.

The Role of Ferritin in Assessing COVID-19 Severity

Ferritin is one of the biomarkers requiring special attention; its blood level increases significantly especially in the severe course of COVID-19. Information on the effect of hyperferritinemia on the disease outcome is very contradictory as are the ideas about the causes of its development.The objective: to study the effect of hyperferritinemia on the disease outcome and analyse the possible causes of its development in severe COVID-19.Subjects and Methods. Data on 479 patients with severe course of coronavirus infection treated in intensive care units (ICU) were retrospectively analyzed. Of them, the proportion of patients with a favorable outcome (Group 1) was 51.0% (n = 241), and with an unfavorable outcome (Group 2) - 49.0% (n = 235). The following parameters were assessed: the levels of ferritin, C-reactive protein, fibrinogen, IL-6, IL-10, IL-18, procalcitonin, complement C5a, total, direct and indirect bilirubin, ALT, AST, and the blood level of lactate dehydrogenase (LDH). The changes of erythrocyte count and hemoglobin blood level were also monitored. In order to form a clear view of iron metabolism, free iron, transferrin, and myoglobin levels were assessed in several patients with high ferritin values (more than 1,500 pg/L).Results. In the unfavorable outcome, ferritin levels increase very significantly, reaching maximum by day 6 of patients' stay in ICU. The difference in the level of ferritin between the groups of survivors and deceased during this period is clear and significant (p = 0.0013). The association of ferritin values with the outcome is detected as early as day 1, but by day 4 it becomes highly significant (the cut-off point is 1,080 pg/l). No data have been obtained that would indicate the association of hyperferritinemia with impaired iron metabolism, the development of hepatic dysfunction, or cellular destruction. In contrast to survivors, those who died on day 6 had elevated IL-6 while C5a level remained unchanged. Conclusions. The rapid increase in ferritin blood levels to 1,000 pg/L or higher is an unfavorable prognostic sign indicating a high probability of a lethal outcome. When assessing genesis of hyperferritinemia in COVID-19, the crucial significance should be attributed to the cytokine storm rather than disorders of iron metabolism or hemotoxic effects of the virus. The persistent increase of ferritin level in blood during 4-6 days of stay in ICU should be considered as a reason to intensify anticytokine therapy.

Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy

Background and Aim: Hepatic encephalopathy (HE) is a neurological disease caused by severe liver disease. Early identification of the risk factor is beneficial to the prevention and treatment of HE. Free bilirubin has always been considered to be the culprit of neonatal kernicterus, but there is no research to explore its role in HE. In this study, we aim to study the clinical significance of the indirect bilirubin-albumin ratio in HE.Methods: A retrospective case-control study of 204 patients with liver failure was conducted. Human serum albumin (HSA) or heme oxygenase-1 (HO-1) inhibitor SnPP (Tin protoporphyrin IX dichloride) was injected intraperitoneally into Ugt1−/− mice to establish a treatment model for endogenous hyperbilirubinemia.Results: IBil/albumin ratio (OR = 1.626, 95% CI1.323–2.000, P &lt; 0.001), white blood cell (WBC) (OR = 1.128, 95% CI 1.009–1.262, P = 0.035), ammonia (OR = 1.010, 95% CI 1.001–1.019, P = 0.027), platelet (OR=1.008, 95% CI 1.001–1.016, P = 0.022), Hb (OR = 0.977, 95% CI 0.961–0.994, P = 0.007), and PTA (OR = 0.960, 95% CI 0.933–0.987, P = 0.005) were independent factors of HE. Patients with a history of liver cirrhosis and severe HE (OR = 12.323, 95% CI 3.278–47.076, P &lt; 0.001) were more likely to die during hospitalization. HSA or SnPP treatment improved cerebellum development and reduced apoptosis of cerebellum cells.Conclusion: The IBil/albumin ratio constitutes the most powerful risk factor in the occurrence of HE, and reducing free bilirubin may be a new strategy for HE treatment.